Christian Bouffioux

Variability in the Recurrence Rate at First Follow-up Cystoscopy after TUR in Stage Ta T1 Transitional Cell Carcinoma of the Bladder: A Combined Analysis of Seven EORTC Studies

OBJECTIVESnTo assess the variability between institutions in the recurrence rate at the first follow-up cystoscopy (RR-FFC) after transurethral resection (TUR) in patients with stage Ta T1 bladder cancer.nnnMETHODSnA total of 2410 patients from seven EORTC phase III trials conducted between 1979 and 1989 were included. Patients with single and with multiple tumors were analyzed separately according to whether or not they received adjuvant intravesical treatment.nnnRESULTSnThe RR-FFC varied greatly between institutions. For patients with a single tumor, it ranged from 3.4% to 20.6% for patients not receiving any intravesical adjuvant treatment and from 0% to 15.4% in those receiving it. In patients with multiple tumors who had adjuvant treatment, it varied between 7.4% and 45.8%. There was a slight decrease over time in the recurrence rate for patients with single tumors, particularly in those receiving adjuvant intravesical treatment.nnnCONCLUSIONSnFor both patients with single and with multiple tumors, the percentage of patients with a recurrence in the bladder at the first follow-up cystoscopy after TUR varies substantially between institutions and cannot be explained by the factors that were assessed. It is suggested that the quality of the TUR performed by the individual surgeons may be responsible.

A combined analysis of European Organization for Research and Treatment of Cancer and Medical Research Council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer

AbstractPurpose: The use of prophylactic agents after primary resection can decrease the incidence of tumor recurrence in patients with stage TaT1 bladder cancer. However, the long-term impact on progression to muscle invasive disease as well as on duration of survival is unknown. A combined analysis of individual patient data from previously performed European Organization for Research and Treatment of Cancer (EORTC) and Medical Research Council (MRC) randomized clinical trials was done in an attempt to answer these crucial questions. We compared immediate versus no adjuvant prophylactic treatment after transurethral resection with respect to disease-free interval, time to progression to muscle invasive disease, time to appearance of distant metastases, duration of survival and progression-free survival.Materials and Methods: All EORTC and MRC prophylactic, randomized phase III trials with primary or recurrent, stage TaT1 transitional cell bladder cancer that compared transurethral resection alone or wit...

Treatment of Superficial Bladder Tumors: Achievements and Needs

Objective: The therapeutic objectives in the initial treatment of superficial tumors are to remove completely the tumor, to assess the need for further therapy and to plan the follow-up. Methods/Results: The EORTC Genitourinary Group assessed the percentage of patients with recurrence at 3 months (3RR) after complete resection of all visible lesions taking into account the institution, the number of tumors at presentation and the year of treatment. The 3RR was considered for 18 institutions. For single tumors, the 3RR varied from 0 to 36% and for multiple tumors from 7 to 75%. The 3RR by number of tumors was 8.7% for single tumors, 21% for 2–5 tumors and 32.2% for >5 tumors. The 3RR by year of entry for single tumors ranged from 21.0 to 43.8% during 1975–1978, from 6.3 to 12.7% during 1984–1986 and from 3 to 5.3% during 1987–1989. For multiple tumors it ranged from 50.0 to 61.5% during 1975–1978, from 20.2 to 27.3% during 1979–1983 and from 14.4 to 24.6% during 1984– 1986. The use of more refined instruments probably led to the decreasing percentage of the 3RR in more recent years, the large variation between institutions remains unexplained. The bladder’s unique location renders its mucosa accessible to instillation of chemotherapeutic and immunotherapeutic agents. Cytostatics can be instilled into the bladder hours after surgery without severe complications. A single early instillation within 6 h after transurethral resection (TUR) in patients with a solitary bladder tumor category Ta/T1G1 to G3 could reduce the recurrence rate per year by nearly 50%. The superiority of any of the commonly used intravesical drugs has never been demonstrated; the time to initiate therapy is important for treatment outcome. Optimal results can be achieved by initiating treatment early (within 24 h after TUR) and for a duration of 6 months, and maintenance (>6 months) for patients with a delayed first instillation (>7 days after TUR). Bacillus Calmette-Guérin (BCG) immunotherapy has been confirmed to be highly effective in the reduction of tumor recurrence, the treatment of residual papillary transitional cell carcinoma and the treatment of carcinoma in situ (CIS). The response rate in the treatment of the papillary disease averages 55%, and for CIS 73%. In the prevention of tumor recurrence the relative benefit of BCG is 45%. A direct prospective randomized comparison of BCG with intravesical chemotherapy has found it to be significantly superior to thiotepa, to doxorubicin and to mitomycin C when only patients with intermediate and high risk for recurrence were treated. In studies including patients with low recurrence risk, no advantage for BCG was found. Clinical trials showed no superiority of BCG immunotherapy to chemotherapy in preventing progression to ≧T2. Conclusions: Investigation of the concept of chemoimmunotherapy up to now lacked evidence of advantages for this approach. Preventive regulatory measures directed to decrease tobacco smoking and some occupational exposures to aromatic amines may contribute to the reduction of bladder cancer. Bladder cancer is a multistep process making this tumor a candidate for chemoprevention. To date, retinoids are the best-studied chemopreventive agents achieving mixed clinical results in superficial bladder tumors. The potent apoptosis-inducing retinoid fenretinide is currently in the phase III trials. The follow-up of patients with all types of superficial tumors must be lifelong; unfortunately cystoscopy cannot be replaced yet by the control of any markers present or not in the urine. There is hope this may change in the near future.

Treatment of Ta, T1 Bladder Tumors: Recent Results of the EORTC-GU Group

Superficial bladder cancer is one of the most frequently encountered tumors in urologic practice. The best management at present is a matter of controversy. Transurethral resection (TUR) remains the treatment of choice, but there is a considerable risk of recurrence of tumors thus treated (50%–70%), as well as a lower risk (10%–15%) of progression to muscle-invasive disease (Kurth et al. 1995). Adjuvant treatment has been advocated for 30 years in order to reduce the number of locally recurrent tumors, the incidence of metastatic disease, and the risk of progression to muscle-invasive disease. Numerous randomized trials have been reported in which the effectiveness of multiple intravesically instilled chemo-and immunotherapeutic agents has been investigated. These adjuvant therapies have been investigated for more than 20 years by the European Organization for Research and Treatment of Cancer (EORTC) Genito-Urinary (GU) Group (Bouffioux 1995). The conclusions drawn from these studies have been: n n1. n nPrimary, solitary, low-stage, low-grade tumors should be resected and should not be treated by adjuvant intravesical therapies. One instillation of a chemotherapeutic agent soon after TUR may favorably influence the recurrence rate. n n n n n2. n nTUR alone results in a higher recurrence rate than TUR followed by instillation therapy, whatever drug is used. n n n n n3. n nThere are no hard data to demonstrate that a superior drug exists, although bacille Calmette-Guerin (BCG) might be superior for high-risk tumors. n n n n n4. n nIt is not possible to conclude from individual trials whether intravesical chemotherapy is able to prevent the occurrence of muscle-invasive disease and metastases.

Endocrinology of normal and pathological development of the prostate

The prostate as much as other accessory sexual glands (e.g., seminal vesicles, bulbourethral glands) has been used for a long time as a model for the study of the mechanism of action of androgens on the regulation of protidic and ribonucleic synthesis toward understanding regulation of the secretory activity and epithelial growth. The prostate is present in mammals only. It produces various components of the spermatic fluid, including fructose, zinc ions, and protides. In human pathology, benign prostatic hypertrophy (BPH) is the most frequent non-malignant proliferative disease.

Original lithotomy positioning for transperineal extracorporeal shockwave lithotripsy for distal ureteric calculi with Tripter X1.

Extracorporeal shockwave lithotripsy (ESWL) has been initially designed for stones located in the kidney and the upper ureter. Our lithotripter is no exception. Its components (the table and the orientation of the semi-ellipsoid reflector) are adapted for the treatment of kidney or lumbar ureter stones. However, the elements forming the unit of treatment (the table, the C-arm and the Tripter) can be modified in such a way that focalization of stones of the lower ureter becomes possible through a perineal exposure. The aim is to avoid the pelvic bone shield while a good focalization of the stone is realized. From June 1989 to March 1991, 35 patients were treated for distal ureteric stones by ESWL in this original positioning.

Belgian experience with the Direx Tripter X1.

In the Department of Urology of the University of Liege Medical Center, 207 kidneys were treated by shock wave lithotripsy using the Direx Tripter X-1. Various forms of anesthesia/sedation were used. A 93% fragmentation rate was obtained, and 80% of patients were stone free at three months. Thirteen percent of cases required multiple treatments. In 6% of cases, post-ESWL auxiliary procedures were performed. No significant complications were encountered. Utilization of the Tripter X-1, equipped with C-arm fluoroscopy, is quite simple, and the apparatus is reliable. This type of lithotripter provides affordable treatment of upper urinary tract calculi in any hospital, with results comparable to those obtained with more sophisticated and expensive machines.